Standard Operating Procedure for Alarms and Alerts Handling During Culture in Biosimilar Manufacturing

Department	Biosimilars
SOP No.	SOP/BS/149/2025
Supersedes	SOP/BS/149/2022
Page No.	Page 1 of 9
Issue Date	04/05/2025
Effective Date	06/05/2025
Review Date	04/05/2026

1. Purpose

To define a standardized approach for handling, investigating, and documenting alarms and alerts generated during culture operations in biosimilar upstream processing. This ensures process continuity, product quality, and GMP compliance.

2. Scope

This SOP applies to all automated bioreactor systems, incubators, culture monitoring systems, and support utilities generating audio/visual or software-based alarms during biosimilar manufacturing.

3. Responsibilities

• Production Operators: Monitor alarms and alerts, take immediate action as per instructions, and document the event.
• Engineering: Investigate equipment-related faults and restore functionality.
• QA: Review alarm incidents and approve CAPA if critical deviations are involved.

4. Accountability

The Head of Manufacturing is accountable for ensuring alarm handling procedures are followed, documented, and reviewed for compliance and process robustness.

5. Procedure

5.1 Types of Alarms and Alerts

1. Process Alarms: Deviations in setpoint parameters like temperature, pH, DO, agitation speed.
2. Equipment Alarms: Malfunctions such as motor failure, pump stoppage, sensor disconnection.
3. System Alerts: Communication errors, power backup switching, minor warnings not affecting critical control.

5.2 Alarm Detection and Initial Response

1. All alarms shall trigger a visual or audible indicator and log entry in SCADA/BMS/PLC system.
2. Operators must acknowledge the alarm within 2 minutes.
3. Review the alarm message, timestamp, and parameter deviation details.

5.3 Immediate Actions

1. If within alert range: monitor closely, inform supervisor, and continue process.
2. If alarm is critical:
   • Pause process if required.
   • Isolate the affected system.
   • Initiate corrective action such as resetting the controller or switching to backup equipment.
3. Log the alarm in Annexure-1: Alarm Handling Log and inform QA if it may impact batch quality.

5.4 Investigation and Documentation

1. Engineering to perform system diagnostics and identify root cause.
2. QA to initiate deviation if alarm led to parameter excursion or batch impact.
3. Attach alarm printout and controller logs to Annexure-2: Alarm Investigation Form.

5.5 Closure and Review

1. After resolution, reset system and resume operations as per QA approval.
2. QA to trend alarms monthly and assess reoccurrence for system improvements.

6. Abbreviations

• SCADA: Supervisory Control and Data Acquisition
• QA: Quality Assurance
• PLC: Programmable Logic Controller
• BMS: Building Management System

7. Documents

1. Alarm Handling Log – Annexure-1
2. Alarm Investigation Form – Annexure-2

8. References

• ICH Q10 – Pharmaceutical Quality System
• EU GMP Annex 11 – Computerized Systems
• FDA CFR Part 211 – Subpart D: Equipment

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Alarm Handling Log

Date	System	Parameter	Alarm Type	Action Taken	Operator
03/05/2025	Bioreactor-5	DO	High Alarm	Reduced airflow	Ajay Verma

Annexure-2: Alarm Investigation Form

Alarm ID	Date	Description	Root Cause	Corrective Action	QA Review
AL-DO-037	03/05/2025	DO spike > 85%	Flow valve stuck open	Replaced actuator	Reviewed

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
04/05/2025	2.0	Expanded alarm classification and added SCADA integration steps	System enhancement